The overall hypothesis of this proposal is that genetic and environmental factors are involved in normal human craniofacial and limb development and are risk factors for these disorders. The goal of this proposal is to determine those genetic and environmental factors involved in human craniofacial and limb development. The common human craniofacial conditions of craniosynostosis, oral clefts, and mandibulofacial dysostosis, and their associated limb abnormalities will be studied in over 500 patients in the Mid-Atlantic Region during the next five year period.